Phillygenin glucuronide derivatives are active ingredients extracted from dried leaves of Oleaceae Forsythia suspensa(Thunb.) vahl. Forsythia serving as a traditional Chinese medicine has been applied for a history of two thousand years, and was began to be present in Shennong's Herbal Classic. The Shennong's Herbal Classic indicated as follows: “the forsythia is mainly used for treating chills and fever, carbuncles, malignant sores, stagnation of pathogenic heat, and scrofula.” Since Murakami extracted oleanolic acid from forsythia fruits first, more than sixty components in the forsythia and congeneric plants thereof have been reported. The components mainly contain terpenes, phenethyl alcohol and glycosides thereof, lignans, flavonoids and some alcohol, ester, ether, ketone and other compounds.
Lignan components in the forsythia mainly refer to lignanolide and bisepoxylignans. Nishibe et al. extracted arctigenin, mataresinol, arctiin and matairesinoside from the forsythia in 1978. Tsukamoto et al. extracted phillygenin, (+)-pinoresinol, phillyrin, (+)-pinoresnol-β-D-glucoside and (+)-epinoresinol-4-O-glucoside from the forsythia fruits in 1985. Liu Donglei et al. extracted (+)pinoresinolmonomethylether-β-D-glucoside) from the forsythia fruits in 1997. Recent biosynthesis study shows that a lignan precursor in the forsythia is coniferyl alcohol. For lignan and glycosides thereof in known forsythia, 3,3′ totally substituted by methoxy, 4,4′ may be hydroxyl, substituted by methoxy or form glycosides with saccharides.
Three phillygenin glucuronide derivatives are first discovered from forsythia leaves. Glucuronic acid derivatives have good activities, e.g. artemisinin glucuronic acid derivatives (Efficient Preparations of the β-Glucuronides of Dihydroartemisinin and Structural Confirmation of the Human Glucuronide Metabolite. Paul M. O'Neill, Feodor Scheinmann, Andrew V. Stachulski, James L. Maggs, and B. Kevin Park. J. Med. Chem., 2001, 44(9), pp 1467-1470); edaravone glucuronic acid derivatives (Synthesis of the metabolites of a free radical scavenger edaravone (MCI-186, Radicut™). Kazutoshi Watanabe, Masao Taniguchi, Masaki Shinoda. Redox Report, Vol. 8, No. 3, 2003, 157-161), combretastatin A-1 glucuronic acid derivatives (Regio- and Stereospecific Synthesis of Mono-β-d-Glucuronic Acid Derivatives of Combretastatin A-1.Rajendra P. Tanpure, Tracy E. Strecker, David J. Chaplin, Bronwyn G. Siim, Mary Lynn Trawick and Kevin G. Pinney J. Nat. Prod., 2010, 73(6), pp 1093-1101); resveratrol glucuronic acid derivatives (WANG LAIXI; Heredia, A.; Song, H J; ZHANG ZHAOJUN; Y U BIAO; Davis, C.; Redfield, R. Resveratrol glucuronides as the metabolites of resveratrol in humans: Characterization, synthesis, and anti-HIV activity. J. Pharm. Sci. 2004, 93(10), 2448-2457); curcumin glucuronic acid derivatives (K. S. Psrvathy, M. Sc. University of Mysore. 2009), etc. Therefore, preparation methods of the three phillygenin glucuronide derivatives are researched, and pharmacological study is carried out.